Anti-nucleic acid antibodies are involved in the pathologic mechanisms in human systemic lupus erythematosus and the murine models. The degree of this antibody restriction is unknown. We propose to examine the heterogeneity of the anti-nucleic acid antibody response i.e., spontaneous antibodies to DNA and poly A. Further, we will study and define the system of idiotype-anti-idiotype interactions with regard to these antibodies. Examination of the actions of idiotype and anti-idiotype in serum as well as their role as surface receptors should provide valuable insights into the immunological regulation of anti-DNA and anti-poly A antibodies. We shall investigate the ability of anti-idiotypic antisera to suppress the antibody response to DNA and poly A. These experiments offer a potentially valuable therapeutic approach for the treatment of human systemic lupus erythematosus.